The objective of this project is to develop potential approaches to the therapy of brain and spinal cord injury. One approach is to limit the production or increase the degradation of chondroitin sulfate proteoglycans (CSPGs). We have published studies that demonstrate significant changes in the regulation of CSPGs in response to controlled cortical impact traumatic brain injury. These studies show that TBI causes astrogliosis and an increase in the production of CSPGs in the gliotic area, but also reduces CSPGs in preirneuronal nets. We published a study that demonstrated that the binding of receptor protein tyrosine phosphatase sigma, which has been identified as a potential receptor for CSPGs, is not dependent on the presence of CSPGs in the brain. Thus suggests that they bind to some other entity, which we are in the process of idenfifying. We are conducting studies to understand the changes in cell motility and ECM formation in fibroblasts derived from patients with mutations in chondroitin sulfotransferases. We hope to develop techniques to restore normal function to these fibroblasts.